Poly (ADP-ribose) synthetase mediates intestinal mucosal barrier dysfunction after mesenteric ischemia.

摘要: Peroxynitrite-mediated DNA strand breaks trigger poly (ADP-ribose) synthetase (PARS) activation, resulting in intracellular energetic failure and organ dysfunction. We investigated the role of PARS activation on inflammatory functional response intestine to mesenteric ischemia-reperfusion injury. Anesthetized rats exposed 15 min occlusion superior artery showed an increased mucosal activity (ex vivo incorporation radiolabelled NAD+ gut scrapings) as soon 10 after reperfusion. During first 30 reperfusion, significant damage developed, well hyperpermeability a 4000 MW fluorescent dextran (FD4). These alterations were significantly reduced by treatment with NO synthase inhibitor L-NMA, which blocks production peroxynitrite, inhibitors 3-aminobenzamide nicotinamide, whereas they markedly enhanced glutathione depletor L-buthionine-(S,R)-sulfoximine. Also, inhibition ileal neutrophil infiltration (myeloperoxidase activity) at 3 h In second set experiments, effects or ischemia followed reperfusion evaluated knockout wild-type mice. Significant protection against histological damage, infiltration, barrier (evaluated mucosal-to-serosal FD4 clearance everted sacs incubated ex vivo) was noted mice, who also remote organs, shown lesser lipid peroxidation (malondialdehyde formation) lung liver. conclusion, plays crucial mediating intestinal injury dysfunction early late phases Pharmacological may be novel approach protect tissues from reperfusion-related damage.